When doctors don't know what's wrong

Summary

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Unexplainable (Vox): When doctors don't know what's wrong

Release Date: July 15, 2026
Host: Bert Pinkerton
Guest: Alexandra Sifferlin, Deputy Science Editor at The New York Times and author of The Elusive Body: Patients, Doctors, and the Diagnosis Crisis

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Episode Overview

This episode of Unexplainable delves into the ongoing mystery of medical misdiagnosis and undiagnosed diseases, focusing on why it can be so hard for patients to get answers about their health. Science journalist Alexandra Sifferlin shares the story of Louise Proctor—a woman whose mysterious condition went unresolved for decades—and explores what her journey reveals about the broader problems in diagnosis and how collaborative, persistent scientific effort can begin to address them.

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Key Discussion Points & Insights

Prevalence and Impact of Diagnostic Errors

• Prevalence: Nearly everyone will experience at least one diagnostic error in their lifetime, as reported by the National Academies of Sciences, Engineering and Medicine (01:43).
  • “Nearly every person will experience at least one diagnostic error in their life time, sometimes with devastating consequences.” — Alexandra Sifferlin (01:55)
• Severity Spectrum: Not every diagnostic error is catastrophic, but cumulative effects are substantial (02:01).

Case Study: Louise Proctor’s Diagnostic Odyssey

Louise’s Early Symptoms and Frustrations

• Onset: Louise, who grew up in rural Kentucky and led an active life, experienced abrupt and intense leg pain at age 25 (04:19).
• Dismissal by Doctors: Initial medical advice was generic (“just be exercising more,” “maybe early stage arthritis”) and unhelpful (05:07, 05:09).
• Isolation: Louise felt disbelief and even suspicion from those around her, especially when requesting accommodations like a wheelchair, since her symptoms were invisible to others (05:29–05:58).
• Time Without Diagnosis: Her struggle lingered for decades, compounding her frustration, pain, and uncertainty (05:26–06:11).

The Power and Pain of Having a Diagnosis

• Louise’s daughter Suzanne was diagnosed with cystic fibrosis and died young, but the diagnosis provided the family understanding and community support (06:22–07:25).
  • “Diagnosis gave people a context to understand what was happening … and to support her and her family.” — Alexandra Sifferlin (07:25)

Breaking Point and Breakthrough

• After Suzanne’s death, Louise’s pursuit intensified; she demanded action after years of being dismissed (07:50).
• A pivotal MRI revealed extensive calcium buildup in Louise’s legs, validating her symptoms and sparking real investigation (08:24–08:44).
  • “I had never seen this level of calcification in the legs of someone who’s alive…” — Lab technician (08:55)
• The condition was so rare, even specialists were perplexed (09:10).

Family Pattern: Is it Genetic?

• Louise’s siblings manifested similar symptoms, raising questions about a familial or genetic disorder (10:35).
• Her case was eventually referred to the NIH’s brand-new Undiagnosed Diseases Program (13:13).

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NIH’s Undiagnosed Diseases Program (UDP): A Model for Complex Diagnoses

How the UDP Works

• Accepts medically mysterious or complex cases from across the U.S.; only a minority get accepted (13:26–13:56).
• Team-based diagnostic approach: experts from various fields collaboratively review histories, perform tests, synthesize findings, and maintain long-term engagement (14:54–16:23).
  • “There’s this sort of commitment that this team is going to be with you on this journey, even if it is going to continue to take a long time…” — Alexandra Sifferlin (16:23)

Louise’s Diagnosis: Science Meets Serendipity

• A postdoc’s prior research on mice missing the CD73 gene led to identifying the Proctors’ disorder as a deficiency of CD73 (16:51–17:52).
  • “It was an incredible coincidence, but also underscored how much can be gained by having this bigger team approach…” — Co-host (17:52)
• The disease was formally named arterial calcification due to deficiency of CD73, or ACDC (18:26–18:33).
  • “They all had this newly named disease called arterial calcification due to deficiency of CD73—also known as ACDC for short.” — Alexandra Sifferlin (18:26)
• Today, an estimated 20 people worldwide have been identified with ACDC (19:15).

Ongoing Impact

• The postdoc who spotted the correlation (Dr. Cynthia St. Hilaire) now runs her own lab focusing on CD73 and peripheral arterial disease (19:42–19:48).
• The team approach emerges as a gold standard for complex, unsolved medical mysteries.

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Broader Lessons from Louise’s Story

Diagnostic Delays Resonate Beyond Rare Disease

• Many patients face the same systemic issues with common as well as rare conditions—long waits, rushed appointments, doctor inattentiveness, lack of continuity (20:14–21:34).
  • “I was in there for maybe 10 minutes … and I don’t feel like they were listening to me.” — Patient accounts (21:13)
• Doctors share similar frustrations: too many patients, little time, burdened by electronic health records (21:47–22:18).
  • “I wish I had more time to review that patient’s medical record, or… to really sit with the information provided and try to piece it together.” — Physician perspective (22:14–22:18)
• Lack of care coordination: Patients often play the role of record-keeper, shuttling binders of information between disconnected specialists (22:42–23:21).

What Works (and What Can Change)

• The UDP’s model—collaborative, coordinated, persistent, time-intensive—contrasts sharply with most of the current U.S. healthcare system (23:21–24:41).
• Even modest versions or adoption of its structure at other centers or for more common conditions may improve outcomes (24:07–24:30).
  • “Physicians need somewhere or someone to send cases that they simply don’t … have the time to figure out.” — Alexandra Sifferlin (24:17)
• Other clinics, such as Dr. Lisa Saunders’ at Yale (noted for her long Covid and diagnosis work), exemplify how even a few extra minutes and organized teamwork can make a profound difference (25:03–25:30).

The Limits and Importance of a Diagnosis

• For the Proctors, the diagnosis brought clarity, support, and knowledge—even as there’s still no cure (25:48–27:28).
  • “A diagnosis without a cure, what does that really get you?” — Bert Pinkerton (26:09)
  • It brings practical benefits: understanding, community recognition, and answers about heritability (26:33–26:47).
• The value of giving a name to the unknown, especially for legitimizing needed accommodations and improving quality of life (27:43–28:17).
  • “I have this ultra-rare condition, it’s ACDC… This is why they happen. And it helps people around them understand.” — Bert Pinkerton (27:48–28:08)

The Emotional Reality of Medical Uncertainty

• The episode closes with a reflection on how medicine’s inherent uncertainty is psychologically difficult for patients—but empathy, engagement, and persistent searching for answers matter immensely (29:12–29:26).
  • “There’s never ever going to be a time where there’s no uncertainty in medicine ... We do have to become a little bit more comfortable in the uncertainty. But ... people really do desire answers—or … some kind of commitment that someone’s going to sit with their questions … and try to provide a more human experience.” — Bert Pinkerton (29:12–29:29)
  • “Even bad news is at least an answer.” — Alexandra Sifferlin (28:22)

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Notable Quotes & Memorable Moments

• “Nearly every person will experience at least one diagnostic error in their lifetime, sometimes with devastating consequences.” — Alexandra Sifferlin (01:55)
• “It was sort of like this diagnosis gave people a context to understand what was happening to this girl and to support her and her family.” — Alexandra Sifferlin (07:25)
• “I had never seen this level of calcification in the legs of someone who’s alive, much less someone who is young and otherwise seems very healthy.” — Lab technician (08:55)
• “There’s this sort of commitment that this team is going to be with you on this journey, even if ... we can’t quite figure it out yet either, because we don’t have the technology available yet.” — Alexandra Sifferlin (16:23)
• “It was an incredible coincidence, but also underscored how much can be gained by having this bigger team approach…” — Co-host (17:52)
• “A diagnosis without a cure, what does that really get you?” — Bert Pinkerton (26:09)
• “Even bad news is at least an answer.” — Alexandra Sifferlin (28:22)
• “There’s never, ever going to be a time where there’s no uncertainty in medicine … but … people really do desire answers, or … some kind of commitment that someone’s going to sit with their questions and … try to provide a more human experience…” — Bert Pinkerton (29:12–29:29)

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Timestamps for Key Segments

• 01:43 — Prevalence of diagnostic errors in the U.S.
• 03:44 — Introduction to Louise Proctor’s story
• 05:26 — Louise’s undiagnosed suffering over decades
• 06:22 — Daughter’s cystic fibrosis diagnosis highlights power of having a name for an illness
• 08:24 — Breakthrough: Imaging finally reveals abnormal calcium buildup
• 10:35 — Similar symptoms in Louise’s siblings; question of genetic disease
• 13:13 — The NIH’s Undiagnosed Diseases Program (UDP) enters the case
• 16:51 — The pivotal postdoc and the role of CD73 in diagnosis
• 18:26 — Official diagnosis: ACDC (arterial calcification due to deficiency of CD73)
• 19:55 — Takeaways: collaboration, long-term engagement, and lessons for broader healthcare
• 21:06–22:18 — Systemic causes for diagnostic errors: time pressures, care fragmentation
• 23:21–24:41 — UDP as a model for care coordination in future medical systems
• 25:48 — The bittersweet outcome: diagnosis without cure, but power in knowledge and ongoing research
• 28:22 — Emotional impact: uncertainty, answers, and the human experience of medicine

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Conclusion

Louise Proctor’s three-decade medical mystery spotlights not just the ordeal of the undiagnosed, but deep, systemic problems in healthcare’s approach to diagnosis—problems that affect everyone from rare disease sufferers to ordinary patients. The episode champions coordinated, team-based diagnostic models—like those pioneered by the NIH’s Undiagnosed Diseases Program—as essential for unraveling complex medical puzzles and bringing dignity, validation, and sometimes hope, even in the absence of a cure. Ultimately, a diagnosis, even imperfect or incomplete, brings relief in its own right, offering recognition, context, and a renewed path forward.

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Book mentioned:
The Elusive Body: Patients, Doctors, and the Diagnosis Crisis by Alexandra Sifferlin

For further information or to share your own story:
Contact: unexplainablevox.com

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Transcript

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[Alexandra Sifferlin]

As a journalist covering health and science, Alexandra Sifferlin got used to a very specific kind of email from readers.

[Bert Pinkerton]

One of the top things that readers would email me about was their personal experiences with trying to find an accurate and timely diagnosis.

[Narrator/Interviewer]

They tell her how hard it was to get answers about what was going on with their health, and it happened

[Co-host/Commentator]

with such frequency that I became very

[Bert Pinkerton]

interested in understanding what was going on here.

[Narrator/Interviewer]

So she looked around for some numbers, like how many people have had problems getting a diagnosis, or how many people have gotten an incorrect or a delayed diagnosis? It's hard to answer those questions exactly, but there have been some attempts to gather data on this.

[Co-host/Commentator]

One of the best versions was this

[Bert Pinkerton]

big report released in 2015 by the National Academies of Sciences, Engineering and Medicine.

[Co-host/Commentator]

And they end up concluding that nearly every person will experience at least one

[Bert Pinkerton]

diagnostic error in their life time, sometimes with devastating consequences.

[Narrator/Interviewer]

Now, that does not mean that every person will have a doctor miss a cancerous tumor or something. There is a spectrum here, and some of those errors are less devastating than others. But still, that is a lot of diagnostic error. In her research, Alexandra was also exploring questions about why this was happening, why it was sometimes so hard to get a diagnosis, what even goes into a diagnosis in the first place.

[Co-host/Commentator]

And I realized, you know, there are

[Bert Pinkerton]

so many different elements to this. And it just became a bigger and bigger project.

[Narrator/Interviewer]

Such a big project, in fact, that it turned into a book called the Elusive Patients, Doctors and the Diagnosis Crisis. And as Alexandra got deeper into her research for that book, she started digging into one story in particular. The story of a woman with an incredibly rare disease. That story reflected a lot of the problems that Alexandra was encountering with diagnosis more generally. And so this is unexplainable. I'm Bird Pinkerton, and today on the show, we are doing a book club. Alexandra Sifferlin, author of the Elusive Body, will tell us about this one woman's journey to a diagnosis and how it illuminates both the problems with how we diagnose disease and how we might do a better job of answering people's unanswered health questions.

[Alexandra Sifferlin]

Let's start with an introduction to a woman named Louise Proctor.

[Bert Pinkerton]

Louise Proctor is the eldest of five Proctor siblings who all grew up in very rural Kentucky.

[Co-host/Commentator]

You know, she describes her childhood as pretty ordinary.

[Bert Pinkerton]

She was pretty active. She would play outside with her friends. She was in band.

[Alexandra Sifferlin]

But in 1980, when Louise was 25 years old, her life started to change.

[Bert Pinkerton]

She remembers very specifically this one day

[Co-host/Commentator]

where she's walking during her lunch break

[Bert Pinkerton]

and she's going up a hill, and all of a sudden she experiences this

[Co-host/Commentator]

excruciating pain and a very bizarre sensation whereby it feels as if her legs

[Bert Pinkerton]

are turning to stone. As she describes it, it's like she's

[Co-host/Commentator]

freezing in place and she can't move one step further. And that sort of sensation started happening

[Bert Pinkerton]

with increasing frequency over the course of her life.

[Alexandra Sifferlin]

The amount of time that she could walk without experiencing pain got shorter and the pain got worse. So, of course, she talked to her doctor about it.

[Bert Pinkerton]

The initial diagnoses, if you will, were things like, you probably should just be exercising more. The. Like, this wouldn't be happening if you were a little bit more fit.

[Co-host/Commentator]

Or she would hear things like, maybe

[Bert Pinkerton]

you have early stage arthritis, but she would be prescribed medications and they would have no effect.

[Co-host/Commentator]

And she just felt really frustrated in the unknown and as if her pain

[Bert Pinkerton]

just really wasn't being taken very seriously at all.

[Alexandra Sifferlin]

This lack of a diagnosis went on for decades.

[Co-host/Commentator]

She would talk about how it felt like nobody believed her. And because she otherwise appeared quite healthy, like, this was sort of a sensation

[Bert Pinkerton]

that would come and go.

[Co-host/Commentator]

She just felt like when she did

[Bert Pinkerton]

need accommodations, like she was going to

[Co-host/Commentator]

the airport and needed a wheelchair that, you know, people around her would kind

[Bert Pinkerton]

of look at her like, what are you doing? Like, I just. You're over exaggerating.

[Co-host/Commentator]

And the pain was getting worse. Like the condition is getting worse over time. In addition, because she has no diagnosis,

[Bert Pinkerton]

she has no prognosis, so she has no idea where this is going

[Alexandra Sifferlin]

in the midst of all this. Louise also had two children to take care of. And in 1984, her infant daughter, Suzanne, was diagnosed with cystic fibrosis.

[Bert Pinkerton]

Today, there are promising treatments and therapies, though it is still a very challenging diagnosis.

[Co-host/Commentator]

But at the time, there really weren't any options.

[Bert Pinkerton]

It's a fatal disease.

[Co-host/Commentator]

And so, you know, tragically, her daughter

[Bert Pinkerton]

does end up dying of cystic fibrosis when she's a young teenager.

[Alexandra Sifferlin]

This was devastating for Louise. But as Alexandra noted, Suzanne's experience also showed the power of a diagnosis. Even though it was terrible, the people in Louise's family and in her community knew what was happening to Louise's daughter.

[Co-host/Commentator]

Everybody from teachers to neighbors were there to accommodate them. And when Suzanne did end up passing

[Bert Pinkerton]

away, this whole community fills the hospital. They're there for her. And it was sort of like this

[Co-host/Commentator]

diagnosis gave people a context to understand

[Bert Pinkerton]

what was happening to this girl and to support her and her family.

[Co-host/Commentator]

And so it was interesting for Louise, I think.

[Bert Pinkerton]

I mean, it was awful, but, you know, she was able to sort of see the contrast in what a diagnosis can provide, even if it's not good news.

[Narrator/Interviewer]

After Suzanne's death, Louise redoubled her efforts to get answers about her own situation.

[Co-host/Commentator]

She's really just angry, and she's like, I've had it.

[Bert Pinkerton]

Like, I cannot handle this cosmic grief in addition to physical disability that nobody seems to believe me over.

[Co-host/Commentator]

And so she talks about having this

[Bert Pinkerton]

appointment where she goes to her doctor and she has a total breakdown in the doctor's office, and she's very upset, and she's basically saying, you know, I can't even do my laundry because my

[Co-host/Commentator]

laundry is in the basement and I can't walk downstairs. And so she finally gets some imaging

[Bert Pinkerton]

done of her legs.

[Co-host/Commentator]

And I mean, this is decades since

[Bert Pinkerton]

she has been complaining about this, that she finally gets some real ultrasound related

[Co-host/Commentator]

images, and it's revealed that she does

[Bert Pinkerton]

have very abnormal buildup of calcium in her legs.

[Alexandra Sifferlin]

Alexandra was actually able to speak to the lab technician who did the scans, because this was a small town and the technician was a family friend of Louise's.

[Bert Pinkerton]

And, you know, she mentioned to me,

[Co-host/Commentator]

like, I had never seen this level

[Bert Pinkerton]

of calcification in the legs of someone who's alive, much less someone who is young and otherwise seems very healthy.

[Alexandra Sifferlin]

Basically, if you think of your big blood vessels as highways for your blood, it was like some of Louise's highways were full of big calcium rocks.

[Co-host/Commentator]

And so in some cases, the blood

[Bert Pinkerton]

is still able to kind of go around the rocks. If you will.

[Co-host/Commentator]

But in other cases, her vessels are

[Bert Pinkerton]

so clogged with calcium that what ends

[Co-host/Commentator]

up happening and the reason that she

[Bert Pinkerton]

is still alive is that the vessels

[Co-host/Commentator]

so start sprouting other smaller vessels, basically

[Alexandra Sifferlin]

like little emergency side roads for the blood to move through. Those roads are not as big as the main highway, and because they're not

[Co-host/Commentator]

the size of the highway, it's painful. Like it just simply there's backup.

[Bert Pinkerton]

The blood isn't getting where it needs

[Co-host/Commentator]

to go, and so that's where the

[Bert Pinkerton]

pain is coming from.

[Alexandra Sifferlin]

There were other unusual things about this calcium buildup, but the main thing was that it was there right on the scans, proof that Louise was not making things up.

[Co-host/Commentator]

So now suddenly Louise is being sent to many more specialists and people are really trying and her primary care doctor

[Bert Pinkerton]

is really trying and everyone's really trying to figure this out, but nobody had

[Co-host/Commentator]

seen this before, even the specialists. So it quickly then becomes clear that

[Bert Pinkerton]

Louise is experiencing something very unusual.

[Narrator/Interviewer]

It was also starting to become clear that it wasn't just Louise. Her siblings were beginning to experience strange symptoms too. Her youngest sibling was experiencing the leg freezing issue. Her brothers also had problems. And Louise's doctor was working with her sister Paula as well, who, much like Louise, had pain when she walked on treadmills for extended periods of time. So what did this mean, right? What did it mean for the siblings? If it was genetic, what did it mean for their kids? Were their kids at risk? What was the problem here? It wasn't clear how Louise or her family members were going to get answers to these questions until Louise's case wound up in front of a special group at the National Institutes of Health. More on that after the break.

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But it still doesn't account for her other symptoms. No, but it does tell us something, though I have no idea what.

[Alexandra Sifferlin]

In 2009, Louise's case was reviewed by a group known as the Undiagnosed Diseases

[Co-host/Commentator]

Program, which at the time was a

[Bert Pinkerton]

very new program that the NIH was running.

[Alexandra Sifferlin]

It was a successful program, and in the years since, the NIH has actually built on it and turned it into something called the Undiagnosed Diseases Network, a rare disease investigation unit.

[Co-host/Commentator]

Essentially, they were taking some of the

[Bert Pinkerton]

most complicated medical mysteries that doctors were referring to them across the country, and

[Co-host/Commentator]

geneticists, neurologists, all sorts of physicians would come together and try to crack the

[Bert Pinkerton]

case as a team.

[Alexandra Sifferlin]

Right from the beginning, the program got a lot of applicants and could not accept them all. But Louise's case did get accepted, in part because it seemed quite unique, in part because it seemed like genetics were involved, and in part because the program was interested in cases that seemed broadly

[Co-host/Commentator]

relevant, cases where even if this turns

[Bert Pinkerton]

out to be a very rare condition,

[Co-host/Commentator]

we think that there's something to be

[Bert Pinkerton]

learned from that condition that could apply across the board.

[Alexandra Sifferlin]

Louise clearly had an issue related to her blood vessels, and issues related to

[Narrator/Interviewer]

blood vessels are extremely common.

[Co-host/Commentator]

So they had a feeling, you know, if we could crack this case, maybe the rare condition that these siblings are

[Bert Pinkerton]

experiencing will have something to say about the wider issue of arterial diseases.

[Narrator/Interviewer]

And once the case was accepted, the program really kicked into gear.

[Co-host/Commentator]

They're coming at it from this very

[Bert Pinkerton]

unique method where they take experts from different fields, and even before a patient arrives at the clinic, they look through their medical history.

[Co-host/Commentator]

They look through the letters that typically a doctor sends. Sometimes the patient sends a letter themselves

[Bert Pinkerton]

or a family member.

[Co-host/Commentator]

They read through all of that and

[Bert Pinkerton]

they come up with a plan.

[Narrator/Interviewer]

The plan in Louise and her sister Paula's case involved them going into the NIH getting a variety of tests. So there were a bunch of different types of scans, but also genetic tests. And then their other siblings were tested too, as well as their parents.

[Co-host/Commentator]

So when they have all these results back, all of these NIH scientists or

[Bert Pinkerton]

clinicians, what have you, they're, you know, experts in their particular field come together and through that process, they try to come to a diagnosis or a conclusion.

[Narrator/Interviewer]

There were a few possible outcomes for this process. Either the researchers would be able to come up with some kind of an answer, maybe this is such and such particular disease, or this is a new disease that we have not seen before.

[Alexandra Sifferlin]

Or as does happen, the researchers, despite

[Narrator/Interviewer]

their best efforts, still wouldn't be able to get to a firm diagnosis.

[Co-host/Commentator]

But once you're in this program, you're invited back every single year.

[Bert Pinkerton]

So that's another element that I think is really important is there's this sort

[Co-host/Commentator]

of commitment that this team is going

[Bert Pinkerton]

to be with you on this journey, even if it is going to continue to take a long time, because we can't quite figure it out yet either,

[Co-host/Commentator]

because we don't have the technology available yet. You might be a case that's sort of on the edge of current medical

[Bert Pinkerton]

knowledge, but the hope is that over time we will be able to figure it out, we'll do further investigation, and perhaps we will ultimately reach a diagnosis together.

[Alexandra Sifferlin]

In Louise's case, though, a team came together and then there was a bit of serendipity. There happened to be a postdoc on the team who had done her PhD thesis on mice. She was studying what happened when those mice were missing a particular gene. And it gets a little complicated, but basically when that gene was missing, it resulted in a strange pattern in the mouse's blood vessels that kind of matched the strange calcification pattern in Louise's family.

[Co-host/Commentator]

So they thought that was very intriguing, but were also like, what are the odds that this random thing that the postdoc had been studying would be relevant to this case? It turns out it was very relevant.

[Alexandra Sifferlin]

Once they went through all the tests and the data, they discovered that the Proctor's condition was very much related to the postdocs research, which helped them figure out that the problem here was a deficiency of an enzyme called CD73.

[Co-host/Commentator]

And that was like, you know, in some ways just an incredible coincidence, but in other ways, I think just underscored how much can be gained by having this bigger team approach where you're including people who have different insights, different areas of research, they've come across different things, and through that you end up raising potential, you know, possibilities that you wouldn't have otherwise.

[Narrator/Interviewer]

And so after 30 years, Louise Proctor finally got a Diagnosis. And her siblings finally got a diagnosis.

[Alexandra Sifferlin]

They all had this newly named disease called arterial calcification due to deficiency of

[Narrator/Interviewer]

CD73, also known as ACDC for short.

[Co-host/Commentator]

You know, it's so fun to hear them talk about it, because in so many ways, they were just amazed that

[Bert Pinkerton]

anyone had taken it this seriously.

[Co-host/Commentator]

Like, to have gone to the nih, to have undergone all of these tests, to know that this entire team of

[Bert Pinkerton]

just really smart, dedicated scientists were focusing so much attention on this thing that they had gone decades experiencing with really, you know, not feeling like they were getting any support.

[Alexandra Sifferlin]

There's a lot to take away here. In 2011, the researchers published their findings about this disease. They'd found a few other people that had it. Alexandra says the estimate is now 20 people worldwide. But the postdoc who spotted the connection to her thesis is actually still studying it. She's gone on to open her own lab where she studies CD73 and peripheral arterial disease full time.

[Co-host/Commentator]

And her whole research has been informed

[Bert Pinkerton]

by this and with the goal to

[Co-host/Commentator]

develop more treatments, hopefully for AC dc,

[Bert Pinkerton]

but also for diseases of the arteries in general.

[Alexandra Sifferlin]

But in Alexandra's reporting, some of the biggest takeaways might be less about this one specific disease and more about what we might learn from the Undiagnosed Diseases Network. She says there are lessons to be learned here, even if we're trying to diagnose more regular things.

[Bert Pinkerton]

The issues related to getting a diagnosis

[Co-host/Commentator]

for a rare disease are actually, in many ways the same issues that people

[Bert Pinkerton]

run into if they're trying to get diagnosed with something that is not rare.

[Co-host/Commentator]

People are dealing with and complaining about

[Bert Pinkerton]

the same issues with the healthcare system.

[Alexandra Sifferlin]

Like, I think it's possible to see Louise's story, for example, and think that as soon as she got the right scans and tests, doctors were able to find solutions for her. But not every disease shows up on a scan. And Alexandra says that in one of the reports she read actually warned against the idea that scans or tech would solve everything. Instead, she says, diagnostic error is this thorny, complex problem connected to a lot of different systemic issues.

[Narrator/Interviewer]

So.

[Alexandra Sifferlin]

So, for example, one thing she encountered over and over when she talked to patients who'd had a diagnostic issue was the problem of time.

[Bert Pinkerton]

They would say it took me forever to get a doctor's appointment. Then I finally got the appointment, and I was in there for maybe 10 minutes most with the doctor. And during that appointment, the doctor was looking at their computer the entire time, typing into it, and I don't feel like they were listening to Me. And that's why I think I didn't get the correct diagnosis to start.

[Co-host/Commentator]

And then I would go and talk to physicians, and I would say, from your perspective, what do you think are some of the factors that play into

[Bert Pinkerton]

situations where you might have gotten the diagnosis wrong or you just couldn't quite figure it out?

[Co-host/Commentator]

And I would basically hear the same complaints. They would say, I have to see

[Bert Pinkerton]

20 patients in a given day. I'm only allotted a tiny amount of time.

[Co-host/Commentator]

And during that time, I'm supposed to

[Bert Pinkerton]

be typing information into the electronic health

[Co-host/Commentator]

record, and I feel like I'm not

[Bert Pinkerton]

able to give the patient my full

[Co-host/Commentator]

attention, or I wish I had more

[Bert Pinkerton]

time in that appointment with the patient, or I wish I had more time to review that patient's medical record, or

[Co-host/Commentator]

I wish I had more time to think, to, like, really sit with the

[Bert Pinkerton]

information provided and try to piece it together.

[Alexandra Sifferlin]

In the NIH program, these doctors were

[Narrator/Interviewer]

able to give Louise time not just

[Alexandra Sifferlin]

in the sort of thorough initial meetings, but also in the follow ups that occurred across the years. And that care was also coordinated, which was another factor that Alexandra heard and

[Narrator/Interviewer]

read about as she was trying to suss out the reasons for diagnostic error.

[Co-host/Commentator]

Often patients feel that they themselves are

[Bert Pinkerton]

the ones that have to be in

[Co-host/Commentator]

charge of bringing their entire medical history

[Bert Pinkerton]

from doctor to doctor.

[Co-host/Commentator]

Like, there's not a lot of coordination.

[Bert Pinkerton]

It ends up, you know, one physician may say, I don't have an answer for you, but I'm gonna send you

[Co-host/Commentator]

to this special specialist.

[Bert Pinkerton]

And they're an expert in XYZ and they can be able to help.

[Co-host/Commentator]

But the problem is that the patient

[Bert Pinkerton]

then feels like they're starting from scratch. So they get to that next person.

[Co-host/Commentator]

And they might come with literal binders of information because they just feel like, you know, this doctor isn't talking to this doctor and things are being missed in that handoff.

[Alexandra Sifferlin]

That really stands in stark contrast with

[Narrator/Interviewer]

this undiagnosed diseases model, where doctors get

[Alexandra Sifferlin]

into a room and talk to each other about the patient before the tests are run and then talk about the

[Narrator/Interviewer]

test together again afterwards.

[Alexandra Sifferlin]

Now, Alexandra did tell me that there are a lot of issues that contribute to diagnostic error, like how tired a doctor is when they see you can be a factor, or in, like, a bigger picture sense. It can be hard for some doctors to get feedback on whether their diagnosis was correct or not and to therefore learn from their mistakes. So the undiagnosed diseases model is not going to solve, like, every problem here. But she still thinks it would be useful to borrow from it.

[Bert Pinkerton]

I mean, I would love to see most hospital systems have a version, even if it's much more modest, of the Undiagnosed Diseases Network.

[Co-host/Commentator]

Physicians need somewhere or someone to send cases that they simply don't necessarily have

[Bert Pinkerton]

the time to figure out, or they don't have the technologies available to them to figure out.

[Co-host/Commentator]

But you can't just dump people from one doctor to the next.

[Bert Pinkerton]

And of course, it's never going to be a guarantee that you will get an immediate diagnosis, especially for something very complicated.

[Co-host/Commentator]

But at least you can go somewhere

[Bert Pinkerton]

where you know that they're going to throw everything at the wall and try.

[Alexandra Sifferlin]

Alexandra has seen medical clinics and systems

[Narrator/Interviewer]

that are recognizing the value of getting

[Alexandra Sifferlin]

more people that are involved in a

[Narrator/Interviewer]

patient's care, just kind of talking with each other.

[Alexandra Sifferlin]

And she's even seen people with models that look something like the undiagnosed diseases network.

[Bert Pinkerton]

Dr. Lisa Saunders at Yale, who writes a diagnosis column for the New York Times, for instance, largely her clinic is focused on long Covid.

[Co-host/Commentator]

Her approach, the way that she sets

[Bert Pinkerton]

up her appointments, and the way that she interacts with other experts. It is in many ways very similar to the Undiagnosed Diseases Network.

[Co-host/Commentator]

You know, even just having a little bit more time with patients who have

[Bert Pinkerton]

these more complicated conditions, I think can go a long way.

[Narrator/Interviewer]

Even if every system does learn from the Undiagnosed Diseases model, though, and doctors have the time and the resources and the coordination to come to a diagnosis, that is just the beginning of the story.

[Bert Pinkerton]

To go back to the Proctor siblings,

[Co-host/Commentator]

it's a little bit bittersweet as well, because though they got this diagnosis and

[Bert Pinkerton]

they contributed to medical science because it was the discovery of a completely new

[Co-host/Commentator]

disease, there isn't a cure or really

[Bert Pinkerton]

a very effective treatment yet for acdc.

[Co-host/Commentator]

And I was really interested in that aspect of their story too, because it made me wonder, a diagnosis without a

[Bert Pinkerton]

cure, what does that really get you? Because ultimately you're still experiencing the same

[Co-host/Commentator]

symptoms and you're not getting relief. And, you know, they were. They're honest that that's really frustrating. However, they talk about how with this

[Bert Pinkerton]

diagnosis, they found out that this particular genetic disorder cannot be passed down to their children.

[Co-host/Commentator]

So that was huge. And then two, all of the siblings are really interested in this idea that scientists are going to be able to

[Bert Pinkerton]

learn something potentially from their case that

[Co-host/Commentator]

could inform future care. And lastly, again, this part of the

[Bert Pinkerton]

Undiagnosed Diseases Network ethos of staying with people over time, the hope is that

[Co-host/Commentator]

they will continue to Research them.

[Bert Pinkerton]

The siblings go back every single year to the NIH to go through again a lot of physical exams, tests.

[Co-host/Commentator]

And the hope is that over time

[Bert Pinkerton]

they will find a treatment and they will get relief. And so they feel like this has been worthwhile because they're at least on a path somewhere.

[Alexandra Sifferlin]

Have they talked, do they talk to you at all about just the idea of having a name like something to

[Narrator/Interviewer]

sort of point to and say, yes, this is what I have.

[Alexandra Sifferlin]

Has that changed their lives at all?

[Co-host/Commentator]

Definitely, because you can tell people I

[Bert Pinkerton]

have this ultra rare condition, it's acdc.

[Co-host/Commentator]

And you're able to say, this is

[Bert Pinkerton]

what the symptoms of this disease are. This is why they happen. And it helps. I think people around them understand that,

[Co-host/Commentator]

you know, Louise needs to park really close to the entrance of a restaurant

[Bert Pinkerton]

so it's easier for her to walk

[Co-host/Commentator]

in or she does need to use a wheelchair in the airport, perhaps, or

[Bert Pinkerton]

at places where there's going to be, you know, walking long distances.

[Co-host/Commentator]

And I think having that information is really useful.

[Alexandra Sifferlin]

I think on our show we celebrate the unknown so much. You know, we celebrate like uncertainty. And I think this story has just really driven home for me how devastating and unknown can be and how like, again, even bad news is at least an answer.

[Co-host/Commentator]

Definitely. I think when it's, when it's your

[Bert Pinkerton]

health and you're experiencing really difficult symptoms

[Co-host/Commentator]

or, you know, a lot of people

[Bert Pinkerton]

I interviewed in my book, like it's their children who have something rare or are experiencing a health complication that they can't explain, it's excruciating. There's never, ever going to be a time where there's no uncertainty in medicine. Like, it's such a field for full of that.

[Co-host/Commentator]

And like, we do have to become

[Bert Pinkerton]

a little bit more comfortable in the uncertainty.

[Co-host/Commentator]

But I think ultimately when it comes

[Bert Pinkerton]

to your health, like, people really do

[Co-host/Commentator]

desire answers or if there's not going

[Bert Pinkerton]

to be an answer, some kind of commitment that someone's going to sit with their questions and give them that attention and time and try to provide a more human experience to a medical system that can feel so inhumane.

[Alexandra Sifferlin]

Alexandra Sifferlin is the deputy science editor

[Narrator/Interviewer]

at the New York Times. Her book is the Elusive Inclusive Patients, Doctors and the Diagnosis Crisis. And we only touched really on material in a few chapters of the book. She also writes about topics like AI in diagnosis, long Covid, even the question of over diagnosis. So if you'd like to read more about diagnosis in general, check out our book. This episode was produced by me, Bert Pinkerton. It was edited by Meredith Hodnot. Christian Ayala did the mixing and the sound design. Melissa Hirsch checked the facts. Noam Hassenfeld does our music. Lissa Soep, Valerie Shenkman, Sally Helm and Joanna Solotarov are the fact that hummingbird moths exist and you should look them up. Thanks always to Brian Resnik for co creating the show with me and Noam. Thanks also to Louise Proctor for taking

[Alexandra Sifferlin]

the time to speak to me about the details of her story. And thanks TO thanks to Dr. Cynthia St. Hilaire, who is no longer a postdoc but an associate professor of medicine at the University of Pittsburgh. She took time to explain her work to me and I really appreciate it.

[Narrator/Interviewer]

And if you have thoughts about diagnosis or further topics in this vein that we should dig into, we are@ unexplainableox.com if you would like to support this show and the journalism that Vox does, we would love it if you would become a member. It is very easy to do, just go to Vox.com members. You will get access to all of Vox's journalism, but you will also know that you are supporting all of Vox's journalism. And for those of you who have emailed us to let us know that you signed up because of Unexplainable, just thank you. Thank you so much. Thank you. Also to those of you who have left us a nice review on your podcast page platform or told someone in your life about the show, you are the best. Unexplainable is part of the Vox Media Podcast network and we will be back very soon with another episode about everything that we don't know.

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